1. Field of the Invention
The invention relates to a micro-dispenser for a biological analysis; in particular, the invention relates to a micro-dispenser with replaceable capillary tubes arranged in a high-density array.
2. Description of the Related Art
Reactions between biological molecules exhibit an extremely high degree of specificity. It is this specificity that provides a living cell with the ability to carry out thousands of chemical reactions simultaneously in the same vessel. In general, this specificity arises from the fit between two molecules having very complex surface topologies.
Systems for medical diagnosis often involve a bank of tests in which each test involves the measurement of the binding of one mobile component to a corresponding immobilized component. To provide inexpensive test kits, systems involving a matrix of immobilized spots have been suggested. Each spot includes the immobilized component of a two-component test. The fluid to be tested is typically brought into contact with the matrix.
The matrix is typically constructed by dispensing small quantities of the immobilized component onto a substrate such as glass that has been chemically modified to bind the immobilized component. The amount of material in each spot is relatively small; however, the number of spots may be quite large. Hence, the generation of such an assay plate requires a reliable micro-dispenser that can place the individual spots at predetermined locations with a high degree of precision.
In FIG. 1a and FIG. 1b, a conventional dispenser disclosed in U.S. Pat. No. 6,001,309 is shown. The device 10 has an outer housing 12 that encompasses the capillary assembly. The housing 12 has an opening 14 through which the capillary 16 extends. At the top of the housing is gasket 20. Also shown is the cover 22 employed during cleaning and filling of the device 10. Included in the cover 22 is first conduit 24 for cleaning solvent addition when the system needs to be evacuated or pressurized; second conduit 28 for connecting to a vacuum source; and third conduit 32 for introducing gas pressure. Cover 22 is adjacent to a thread tube 42 that can serve to lock the capillary casing 50 in the housing 12. The threaded tube 42 has a conical receptacle 46 for receiving the sample. After cleaning, the cover 22 is removed exposing the conical receptacle 46, which is then available for receiving a sample. The conical receptacle 46 has a port 48 which meets the capillary, whereby the sample can touch the capillary 16 and by surface tension the sample can move the length of the capillary 16 to fill the capillary. Threaded casing 50 has a notch that extends downward through threaded casing 50 to receive wires 54 for activating the transducer 56. The piezoelectric transducer 56 is proximal to the orifice 60. The walls of the capillary 16 are quite thin, so that they can move with the expansion and contraction of the transducer 56.
FIG. 2 is a schematic flow representation of a system for producing arrays according to U.S. Pat. No. 6,001,309. In FIG. 2, a storage subsystem 300 is shown as an array of racks. Each bin in the rack contains an array of storage well plates 302. A master controller 304 controls the system. Under computer signal, one or more plates 302 are conveyed from the storage area 300 to the next station 306. At the station 306 a robotic arm 308 is under the control of subsystem controller 309. The robotic arm 308 using micropipette tips 310 transfers microliter quantities of liquid from the plate 302 to one or more appropriate jet 312 located at a maintenance and fill station under the control of subsystem controller 315. For reusable jetting devices, the maintenance and fill station has maintenance caps 316. A holder 318 positions the jetting device 312 on a translation bar 320, thereby the jetting device 312 is moved to the test station 322 under the control of subsystem controller 323. If the jetting device 312 passes the test station, it is then moved by means of the translation bar 320 to the jetting position 334 and positioned over the substrate 336 by means of the translation bar 320 and the holder 318. The jetting dispenser is now in position to begin jetting drops to create the array.
Referring to FIG. 3, another conventional dispensing device disclosed in U.S. Pat. No. 6,110,426 is shown. The dispensing device 110 generally includes a reagent dispenser 112 having a capillary channel 114 adapted to hold a quantity of the reagent solution 116. The channel is formed by a pair of members 112a, 112b which are converged at a tip region 118 at the lower end of the channel. At the tip 118, aqueous solution in the channel forms meniscus 120 as shown in FIG. 4a. With the dispenser so positioned, solenoid 122 is activated to draw a piston 124, causing connecting member 126 to move the tip 118 rapidly toward and away from the surface 131 of the substrate 130, making momentary contact with the surface 131. In effect, the tip 118 of the dispenser 112 is tapped against the substrate surface 131. The tapping movement of tip 118 against the surface 131 acts to break the liquid meniscus 120 in the tip channel 114, bringing the liquid in the tip 118 into contact with substrate surface 131. This, in turn, produces a flowing of the liquid into the capillary space between the tip 118 and the surface 131, acting to draw liquid out of the dispenser channel 114, as seen in FIG. 4b. FIG. 4c shows the flow of fluid from the tip 118 onto the substrate surface 131. The figure illustrates that liquid continues to flow from the dispenser 112 onto the substrate surface 131 until it forms a liquid bead 132.
The dispenser must also operate without clogging over a large number of samples. In addition, the dispenser must be able to change samples quickly, as each spot in the matrix requires a different immobilized component.
The dispenser disclosed in U.S. Pat. No. 6,001,309, is reusable; therefore, it must be cleaned and refilled so that the problem of the counter-contamination easily occurs. Furthermore, due to the maintenance time, the whole operation of such a system is troublesome and inconvenient, and the cost is increased.
Similarly, the dispenser disclosed in U.S. Pat. No. 6,110,426 is contact type so that the problem of the counter-contamination also occurs easily.